In the previous works, we reported that ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3) is a selective and potent inhibitor of protease activated receptor (PAR)-4-dependent activation.1,2,3 We also discovered that YD-3 effectively inhibits the low thrombin-induced Ca++ signal and thromboxane production4. Since thrombin and thromboxane play important role in the pathological thrombosis, the ability of YD-3 in selective inhibit thrombin-induced thromboxane production may be of therapeutic benefit for treating thrombotic diseases.
Recently YD-3 and its major metabolite, 4-(1-benzyl-1H-indazol-3-yl)benzoic acid (CHS-6) were found to inhibit vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and tube formation in human umbilial vein endothelial cells (HUVECs). During in vivo assay, they inhibit VEGF-induced angiogenesis in Matrigel plug animal model.5 Therefore, these two compounds are considered as very promising candidates for development of novel anti-angiogenic agents.
The previously unknown N2-regioisomer of YD-3 derivatives were synthesized and some of their anti-angiogenic activities were reported in this paper.
